The structure and function of the oncogene product of the simian sarcoma virus, v-sis, is being analyzed by means of in vitro mutagenesis. Mutations have been introduced into the v-sis coding sequence by site-directed methods. Resulting variants are tested by their ability to transform NIH/3T3 cells in culture using DNA-mediated gene transfer. The coding sequence of the site of polypeptide glycosylation has been altered without affecting the avility of the viral genome to transform. Mutations have also been generated at sites believed to be involved in polypeptide cleavage. The effect of these mutations on the cellular transforming activity of v-sis and on the polypeptide structure is currently being investigated.